2,2-Dimethoxypropane → Methyl 3-cyano-2-phenylpropanoate

HRID 349711

반응식

HRID 349711 반응식
[CH:1]1[CH:6]=[CH:5][C:4]([CH:7]([C:10]([OH:12])=[O:11])[CH2:8]O)=[CH:3][CH:2]=1.COC(OC)(C)C.[CH2:20]([N:22](CC)CC)C.[CH3:27]S(Cl)(=O)=O.[C-]#N.[K+]>CO.[C-]#N.C([N+](CCCC)(CCCC)CCCC)CCC.CN(C=O)C.C(Cl)Cl.C1(C)C=CC(S(O)(=O)=O)=CC=1>[C:20]([CH2:8][CH:7]([C:4]1[CH:5]=[CH:6][CH:1]=[CH:2][CH:3]=1)[C:10]([O:12][CH3:27])=[O:11])#[N:22]

참가 물질

11

반응물 5

HCID 64952,2-DimethoxypropaneHCID 8471TriethylamineHCID 9032Potassium CyanideHCID 10726Tropic acidHCID 31297Methanesulfonyl chloride

생성물 1

HCID 18464584Methyl 3-cyano-2-phenylpropanoate수율 58%

시약·촉매·용매 5

HCID 6101p-Toluenesulfonic acid촉매HCID 165872Tetrabutylammonium Cyanide촉매HCID 887Methanol용매HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매

실험 절차

DL-tropic acid (10 g, 120 mmol), 2,2-dimethoxypropane (12.48 g, 120 mmol) and catalytical amount of p-toluenesulfonic acid (100 mg) were mixed in MeOH (50 ml) and refluxed overnight. The reaction mixture was cooled and concentrated in-vacuo to dryness and then dissolved in ethyl acetate. The organic phase was washed with water, brine and dried with sodium sulfate, and concentrated in-vacuo to dryness. The crude product was dissolved in anhydrous mentylene chloride (150 ml). Triethylamine (7.27 g, 72 mmol) and methanesulfonyl chloride (8.24 g, 72 mmol) were added and stirred at room temperature overnight before it was washed with water, brine and dried with sodium sulfate. The concentrated residue was heated with KCN (5.88 g, 120 mmol) and tetrabutylammonium cyanide (2 g, 7.4 mmol) in DMF at 80° C. for 1 hour. After cooled down to room temperature, reaction mixture was diluted with methylene chloride, washed with water, brine and dried with Na2SO4. After concentration in-vacuo, the crude product was purified by silica flash chromatography (10% ethyl acetate in hexanes) to afford 6.4 g of the desired product as a yellowish solid (58% in three steps). 1H NMR (500 MHz, CDCl3) δ: 7.37 (m, 3 H), 7.27 (m, 2 H), 3.94 (t, J=7.63 Hz, 1 H), 3.73 (s, 3 H), 3.04 (dd, J=16.79, 7.63 Hz, 1 H), 2.81 (dd, J=17.09, 7.63 Hz, 1H).

후처리

  1. temperaturerefluxed overnight
  2. temperatureThe reaction mixture was cooled
  3. concentrationconcentrated in-vacuo to dryness
  4. dissolutiondissolved in ethyl acetate
  5. washThe organic phase was washed with water, brine
  6. dry with materialdried with sodium sulfate
  7. concentrationconcentrated in-vacuo to dryness
  8. dissolutionThe crude product was dissolved in anhydrous mentylene chloride (150 ml)
  9. washwas washed with water, brine
  10. dry with materialdried with sodium sulfate
  11. temperatureAfter cooled down to room temperature
  12. customreaction mixture
  13. washwashed with water, brine
  14. dry with materialdried with Na2SO4
  15. concentrationAfter concentration in-vacuo
  16. customthe crude product was purified by silica flash chromatography (10% ethyl acetate in hexanes)

출처 및 근거

ORD 기록
ord-104f125deae541d4b957c3d38d091bfc
출처 데이터셋
uspto-grants-2007_02
특허 번호
US07179926B2

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